Keratinocyte growth factor-2 products

Abstract

The present invention concerns variants and chemical derivates of keratinocyte growth factor-2 (KGF-2) protein. Also disclosed are nucleic acid molecules encoding such variants, as well as methods for using such variants and chemical derivates to stimulate epithelial cell proliferation.

We claim:  
     
       1. A keratinocyte growth factor-2 (KGF-2) protein selected from the group consisting of: 
       (a) a KGF-2 protein consisting of residues 66 through 208 of the amino acid sequence set forth in SEQ ID NO: 2; and  
       (b) a KGF-2 protein consisting of residues 66 through 208 of the amino acid sequence set forth in SEQ ID NO: 2 and an N-terminal methionine.  
     
     
       2. The KGF-2 protein according to  claim 1 , wherein said amino acid sequence is nonglycosylated. 
     
     
       3. The KGF-2 protein according to  claim 1 , wherein said amino acid sequence is glycosylated. 
     
     
       4. A chemical derivative comprising a water-soluble polymer conjugated to the KGF-2 protein according to  claim 1 . 
     
     
       5. A polynucleotide encoding the KGF-2 protein according to  claim 1 . 
     
     
       6. A vector comprising a polynucleotide of  claim 5  operatively linked to an expression control sequence. 
     
     
       7. A prokaryotic or eukaryotic host cell containing a polynucleotide of  claim 5 . 
     
     
       8. A method comprising culturing the host cell of  claim 7  in a suitable nutrient medium. 
     
     
       9. The method according to  claim 8 , wherein said host cell is an  E. coli  cell. 
     
     
       10. The method according to  claim 8 , wherein said host cell is selected from a baculovirus cell, COS cell or Chinese hamster ovary cell. 
     
     
       11. The method of claims  8 ,  9  or  10  further comprising isolating a keratinocyte growth factor-2 (KG F-2) protein from said cultured cells or said nutrient medium. 
     
     
       12. A pharmaceutical composition comprising a keratinocyte growth factor-2 (KGF-2) protein isolated in accordance with the method of  claim 11  in association with a pharmaceutically acceptable vehicle. 
     
     
       13. A method comprising the step of isolating a keratinocyte growth factor-2 (KGF-2) protein from a host cell containing a polynucleotide of  claim 5  cultured under conditions allowing the expression of the KGF-2 protein by said host cell. 
     
     
       14. The method according to  claim 13  comprising the step of conjugating the isolated KGF-2 protein to a water-soluble polymer to generate a compound capable of stimulating the production of epithelial cells. 
     
     
       15. A method comprising the steps of: 
       (a) culturing a prokaryotic or eukaryotic host cell containing a polynucleotide of  claim 5 ; and  
       (b) maintaining said host cell under conditions allowing the expression of a keratinocyte growth factor-2 (KGF-2) protein by said host cell.  
     
     
       16. The method of  claim 15 , further comprising after step (b) the following step (c): 
       (c) isolating the KGF-2 protein expressed by said host cell.  
     
     
       17. A pharmaceutical composition comprising a keratinocyte growth factor-2 (KGF-2) protein isolated in accordance with the method of  claim 16  in association with a pharmaceutically acceptable vehicle. 
     
     
       18. A KGF-2 protein which is the recombinant expression product of a prokaryotic or eukaryotic host cell containing an exogenous polynucleotide of  claim 5 . 
     
     
       19. A pharmaceutical composition comprising the KGF-2 protein according to  claim 1  in association with a pharmaceutically acceptable vehicle. 
     
     
       20. The KGF-2 protein according to  claim 1 , wherein at least one domain of the constant region of the heavy chain of human immunoglobulin is fused to the C-terminal end of the KGF-2 protein. 
     
     
       21. A recombinant fusion protein comprising the KGF-2 protein of  claim 1  fused to a heterologous protein.